[Results of combined newborn hearing and deafness gene screening in Yuncheng area of Shanxi Province].

OBJECTIVE: To analyze the clinical significance of combined newborn hearing and deafness gene screening in Yuncheng area of Shanxi Province. METHODS: Results of audiological examinations, including transient evoked otoacoustic emission and automatic discriminative auditory brainstem evoked potentials, for 6 723 newborns born in Yuncheng area from January 1, 2021 to December 31, 2021, were retrospectively analyzed. Those who failed one of the tests were considered to have failed the examination. A deafness-related gene testing kit was used to detect 15 hot spot variants of common deafness-associated genes in China including GJB2, SLC26A4, GJB3, and mtDNA12S rRNA. Neonates who had passed the audiological examinations and those who had not were compared using a chi-square test. RESULTS: Among the 6 723 neonates, 363 (5.40%) were found to carry variants. These have included 166 cases (2.47%) with GJB2 gene variants, 136 cases (2.03%) with SLC26A4 gene variants, 26 cases (0.39%) with mitochondrial 12S rRNA gene variants, and 33 cases (0.49%) with GJB3 gene variants. Among the 6 723 neonates, 267 had failed initial hearing screening, among which 244 had accepted a re-examination, for which 14 cases (5.73%) had failed again. This has yielded an approximate prevalence of hearing disorder of 0.21% (14/6 723). Among 230 newborns who had passed the re-examination, 10 (4.34%) were found to have carried a variant. By contrast, 4 out of the 14 neonates (28.57%) who had failed the re-examination had carried a variant, and there was a significant difference between the two groups (P < 0.05). CONCLUSION: Genetic screening can provide an effective supplement to newborn hearing screening, and the combined screening can provide a best model for the prevention of hearing loss, which can enable early detection of deafness risks, targeted prevention measures, and genetic counseling to provide accurate prognosis for the newborns.

Comparison of Intravitreal Anti-VEGF Agents With Laser Photocoagulation for Retinopathy of Prematurity of 1,627 Eyes in China.

Purpose: To compare the efficacies and treatment outcomes of intravitreal anti-VEGF agents and laser therapy in retinopathy of prematurity (ROP). Methods: A retrospective, non-randomized, comparative study of patients diagnosed with type 1 ROP or aggressive posterior ROP (A-ROP) treated with intravitreal anti-VEGF agents or laser therapy as primary treatment at the People's Hospital of Peking University. Results: A total of 1,627 eyes of 862 patients were included. In Group 1, 399 eyes of 204 patients were diagnosed with A-ROP or zone I type 1 ROP. The initial regression of the anti-VEGF subgroup was better than that of the laser subgroup, and the reactivation rate and rate of progression to retinal detachment were lower than those of the laser subgroup. In Group 2, 1,228 eyes of 658 patients were diagnosed with zone II type 1 ROP. The reactivation rate of the laser subgroup was lower than that of the anti-VEGF subgroup. No significant differences were found in the initial regression and the probability of developing retinal detachment. Among the anti-VEGF agents, the reactivation rate in eyes treated with conbercept was much lower than that in eyes treated with ranibizumab. The spherical power and spherical equivalents of eyes treated with laser were significantly higher than those of eyes treated with anti-VEGF agents 1 year after initial treatment. Conclusions: In contrast to laser therapy, anti-VEGF agents as primary treatments have potential advantages for eyes with zone I type 1 ROP and A-ROP. For eyes with zone II type 1 ROP, laser photocoagulation and anti-VEGF agents therapy showed similar efficacy; however, the rate of reactivation with laser therapy was significantly lower than that with anti-VEGF agents. Among the anti-VEGF agents, the reactivation rate was much lower in eyes treated with conbercept than in eyes treated with ranibizumab. Compared to anti-VEGF agents, laser treated eyes had greater trend to myopia.

Foveal structure changes in infants treated with anti-VEGF therapy or laser therapy guided by optical coherence tomography angiography for retinopathy of prematurity.

AIM: To evaluate foveal vessel density (VD) and foveal thickness using optical coherence tomography angiography (OCTA) in retinopathy of prematurity (ROP) children treated with laser photocoagulation or anti-vascular endothelial growth factor (VEGF) injection. Additionally, we assessed the relationship between foveal microvascular anomalies and different therapies in ROP children. METHODS: This was a single-center, retrospective study of patients with a diagnosis of type 1 ROP. Twenty-three eyes (14 patients) treated with anti-VEGF injection and twenty-nine eyes (17 patients) treated with laser coagulation were included in this study. The foveal VD, inner thickness and full thickness were measured at the central 0°, 2° to 8°, and 8° of the retina (centered on the fovea) using OCTA and cross-sectional OCT, respectively. RESULTS: Foveal VD, inner thickness and full thickness were significantly smaller within the central 8° of the retina in ROP children treated with anti-VEGF injection than in those treated with laser photocoagulation (P=0.013, 0.009, 0.036, respectively). The full thickness was also smaller in the anti-VEGF group than in the laser group at the central 0° of the retina (P=0.010). The grade of foveal hypoplasia is lower in the anti-VEGF group than in the laser group (P=0.045). Multivariable analysis did not find any risk factors associated with visual acuity in our study. CONCLUSION: In children with type 1 ROP, the better structural development of fovea in those who were treated with anti-VEGF injection compared with laser photocoagulation are identified. However, visual acuity outcomes are similar 70mo after the treatments.

Systemic conbercept pharmacokinetics and VEGF pharmacodynamics following intravitreal injections of conbercept in patients with retinopathy of prematurity.

BACKGROUND: Data on serum vascular endothelial growth factor (VEGF) and drug levels in patients with retinopathy of prematurity (ROP) following intravitreal injections of conbercept (IVC) are lacking. METHODS: Multicentre, prospective, non-randomised study of patients with aggressive posterior retinopathy of prematurity (APROP) or type 1 ROP who had not received other treatment. All infants received therapy in both eyes plus intravitreal IVC 0.25 mg/0.025 mL in one eye and had at least 6 months of follow-up. Blood samples were collected before and 1 week and 4 weeks after IVC. The main outcome measures were serum conbercept and VEGF concentrations. RESULTS: Forty infants with APROP or type 1 ROP were enrolled. The mean serum VEGF at baseline and 1 week and 4 weeks after a total of 0.25 mg of IVC was 953.35±311.90 pg/mL, 303.46±181.89 pg/mL and 883.12±303.89 pg/mL, respectively. Serum VEGF 1 week after IVC was significantly lower (p<0.05) than baseline, and at 4 weeks after IVC, it was significantly higher (p<0.05) than at 1 week. There was no significant difference (p>0.05) between baseline and 4 weeks. Serum conbercept was below the limit of quantitation (BLOQ) at baseline and 4 weeks and was 19.81±7.60 ng/mL at 1 week. CONCLUSION: Serum VEGF 1 week after IVC was significantly lower than baseline but returned to baseline at 4 weeks. Serum conbercept increased at 1 week and was BLOQ at 4 weeks.

Using random forest to detect multiple inherited metabolic diseases simultaneously based on GC-MS urinary metabolomics.

Inborn errors of metabolism, also known as inherited metabolic diseases (IMDs), are related to genetic mutations and cause corresponding biochemical metabolic disorder of newborns and even sudden infant death. Timely detection and diagnosis of IMDs are of great significance for improving survival of newborns. Here we propose a strategy for simultaneously detecting six types of IMDs via combining GC-MS technique with the random forest algorithm (RF). Clinical urine samples from IMD and healthy patients are analyzed using GC-MS for acquiring metabolomics data. Then, the RF model is established as a multi-classification tool for the GC-MS data. Compared with the models built by artificial neural network and support vector machine, the results demonstrated the RF model has superior performance of high specificity, sensitivity, precision, accuracy, and matthews correlation coefficients on identifying all six types of IMDs and normal samples. The proposed strategy can afford a useful method for reliable and effective identification of multiple IMDs in clinical diagnosis.

Comparison of the outcomes of photodynamic therapy for central serous chorioretinopathy with or without subfoveal fibrin.

BACKGROUND: To compare the outcomes of half-dose verteporfin photodynamic therapy (vPDT) for central serous chorioretinopathy (CSCR) with or without subfoveal fibrin. METHODS: One hundred seventy-three cases of CSCR treated with half-dose vPDT between September 2008 and February 2018 were retrospectively reviewed and classified into two groups: CSCR with subfoveal fibrin (fibrin group) and without subfoveal fibrin (no-fibrin group). The changes in best-corrected visual acuity (BCVA) from baseline and in central macular thickness (CMT) were recorded at 1, 3, and 6 months after the treatment. RESULTS: Forty-eight eyes were included in the fibrin group and 125 eyes in the no fibrin group. There were no statistical differences in the baseline characteristics including age, gender, duration of symptoms, and CMT between the groups. The baseline mean BCVA of the fibrin group was significantly worse than that of the no fibrin group (0.47 ± 0.32 versus 0.32 ± 0.31 in logMAR; p = 0.003). There was no statistically significant difference between the two groups in the improvement of BCVA at each follow-up point (1 month: p = 0.069; 3 months: p = 0.111; 6 months: p = 0.172, respectively) and in the reduction of CMT (1 month: p = 0.367; 3 months: p = 0.767; 6 months: p = 0.496, respectively). In the fibrin group, the rates of complete resolution of the subretinal fibrin at 1, 3, and 6 months after vPDT were 72.9%, 95.8%, 95.8%, respectively. The SRF resolution rate at 1, 3, and 6 months was 72.9%, 89.6% and 91.7% respectively in the fibrin group and was 62.4%, 83.2% and 84.0% in the no fibrin group. There was no significant difference of SRF resolution rate between the two groups at 1 month (p = 0.216), 3 months (p = 0.350), and 6 months (p = 0.228). No ocular adverse event was encountered in both groups. CONCLUSION: Half-dose vPDT was effective and safe for CSCR patients with subfoveal fibrin.

Serum levels of cytokines in infants treated with conbercept for retinopathy of prematurity.

Intravitreal anti-vascular endothelial growth factor (VEGF) agents have revolutionized the treatment of retinopathy of prematurity (ROP); however, there are concerns regarding the potential systemic complications caused by those treatments. This study aimed to determine the serum concentrations of cytokines in infants with ROP and to evaluate the changes in serum VEGF concentrations after intravitreal conbercept (IVC). Sixty infants with ROP treated with IVC 0.25 mg were included. Blood samples were collected before treatment as well as 1 week and 4 weeks after treatment. Serum levels of 45 types of cytokines were measured by a multiplex bead assay. We observed that IVC 0.25 mg in ROP patients suppressed the circulating levels of VEGF-A and VEGF-D as of 1 week after injection, and these growth factor levels returned to baseline at 4 weeks. No significant differences were observed in the serum levels of the other cytokines between baseline and 1 or 4 weeks after IVC.

Comparison of the effectiveness of conbercept and ranibizumab treatment for retinopathy of prematurity.

PURPOSE: To compare the effectiveness of intravitreal conbercept and ranibizumab treatment for retinopathy of prematurity (ROP). METHODS: In this retrospective study, the date of patients with ROP treated with intravitreal conbercept or ranibizumab from July 2012 to March 2018 with at least 12 months of follow-up at the Eye Center in People's Hospital of Peking University were analysed. Regression, progression or recurrence and peripheral retina vascularization were evaluated. RESULTS: In total, 283 eyes (145 infants) with conbercept treatment and 916 eyes (480 infants) with ranibizumab treatment were enrolled. In zone I ROP and aggressive posterior ROP (APROP), the recurrence prevalence was 49.09% (108/220 eyes) and 28.57% (10/33 eyes), and the recurrence interval was 7.87 ± 0.65 (5.5-9.5) weeks and 10.6 ± 1.53 (10.5-13) weeks in the ranibizumab and conbercept groups, respectively. In zone II ROP disease, the recurrence prevalence was 23.56% (164/696 eyes) and 13.31% (33/248 eyes), and the interval of recurrence was 8.40 ± 0.88 (6-10.5) weeks and 11.4 ± 1.35 (11-13.5) weeks in the ranibizumab and conbercept groups, respectively. The recurrence prevalence was significantly higher with ranibizumab in Zone I ROP and APROP (p = 0.006) and Zone II ROP (p < 0.001), and the recurrence interval was significantly longer in the conbercept group than that in the ranibizumab (p < 0.001). There was no significant difference in the rate of retinal vascularization (p = 0.441). CONCLUSION: Conbercept and ranibizumab are effective for treating ROP. Compared with ranibizumab, conbercept resulted in less recurrence and longer treatment intervals.

Association between CFH single nucleotide polymorphisms and response to photodynamic therapy in patients with central serous chorioretinopathy.

PURPOSE: To evaluate the association between single nucleotide polymorphisms (SNPs) in the complement factor H (CFH) gene and response to PDT in patients with CSC. METHODS: 103 eyes from 93 patients with CSC were enrolled from Department of Ophthalmology of the People's Hospital Peking University. Genotyping for selected SNPs in the CFH gene was performed, and multivariate linear analysis was used to identify factors influencing PDT treatment outcomes. Genetics associations between SNPs in the CFH gene and response to PDT in patients with CSC were analyzed. RESULTS: None of the seven SNPs examined in this study (rs800292, rs1061170, rs3753394, rs3753396, rs2284664, rs1329428, and rs1065489) showed significant associations with 1-month outcomes after PDT in patients with CSC (P > 0.05). Baseline BCVA changed at 1 month after PDT (P < 0.001), and baseline retinal thickness was associated with changes in retinal thickness at 1 month after PDT (P < 0.001). Age was significantly associated with resolution of SRF at 1 month after PDT (P = 0.004). CONCLUSIONS: There were no significant associations between SNPs in the CFH gene and 1-month outcomes after PDT in patients with CSC. However, baseline BCVA, baseline retinal thickness, and age were significantly associated with response to PDT in patients with CSC. Larger studies with more power are necessary to further determine whether an association exists between SNPs in the CFH gene and PDT in patients with CSC.

A lower dose of intravitreal conbercept effectively treats retinopathy of prematurity.

Intravitreal Conbercept (IVC) is the latest applied and effective treatment for the management of retinopathy of prematurity (ROP). However, conbercept escapes from the vitreous into the general circulation and reduce systemic VEGF concentrations. Thus, there are concerns about systemic complications, in these premature infants who are developing vital organ systems. This study is to determine whether a low dosage (0.15 mg/0.015 mL) of IVC is effective in the treatment of Zone II Stage 2/3 + ROP. A total of 38 eyes of 20 infants were analyzed retrospectively. We identified treatment effectiveness as complete regression of retinopathy and retinal vascularisation to zone III. The mean gestational age (GA), postmenstrual age (PMA) at treatment and birth weights (BW) were 28.6 ± 2.2 weeks, 39.3 ± 3.0 weeks and 1297.5 ± 429.2 g respectively. Primary effectiveness (react to IVC 0.15 mg alone) was found in 32/38 eyes (84.2%). Secondary effectiveness (a second IVC was required) was found in 6/38 eyes (15.8%). Follow-up continued until 90 weeks' postmenstrual age and showed no recurrences of plus disease or neovascularization. The study suggests 0.15 mg IVC is effective for Zone II Stage 2/3 + ROP, and there is no adverse ocular outcomes during the follow-up period.

iTRAQ-based quantitative proteomic analysis and bioinformatics study of proteins in pterygia.

PURPOSE: To analyze proteins in the tissue of pterygia, and to investigate their potential roles in pterygia, using the comparative proteomic technique of Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) coupled with offline 2DLC-MS/MS, Western-bolt. METHOD: The tissue of pterygia and healthy conjunctiva was collected from 10 pterygia patients (6 females, 4 males; average age was 52 years old; average course of disease was 6 years) in our hospital from September, 2015 to March, 2016. iTRAQ was used to analyze proteins in the patients' pterygia and healthy conjunctiva. Proteins with a fold change of >2. 0 or <0. 5 were considered to be significantly differentially expressed (with corrected p-values of <0. 1). The identified proteins were subjected to subsequent gene ontology analysis using the DAVID database. Then we confirmed the targeted proteins with western-blot. RESULTS: 156 proteins that expressed differently between the pterygia and healthy conjunctiva were identified using iTRAQ analysis. Of these proteins, 18 were down-regulated, and 138 were up-regulated. On the basis of biological processes in gene ontology, the identified proteins were mainly involved in cellular process, metabolic process, developmental process, location, cellular component organization, Among these proteins, matrix Metalloproteinase 10 (MMP-10) and CD34 may have potential roles in the pathogenesis of pterygia. Then we confirmed with Western-bolt that MMP-10 and CD34 were up-regulated in pterygia. CONCLUSION: This study is the first to identify 156 proteins associated with pterygia with iTRAQ technology. Data in our study will aid in providing a better understanding of pterygia.